An ambiguous genitalia in a 46XX female is unlikely to be due to? (AIPG 2011)
|A||Early antenatal exposure to androgens from fetal adrenals|
|B||Placental steroid sulfatase deficiency|
|C||Fetal aromatase deficiency|
|D||Fetal Wnt4 mutation.|
Placental steroid sulfatase deficiency.
An ambiguous genitalia in a 46XX female is unlikely to be due to Placental steroid sulfatase deficiency.
a. Fetal adrenal steroidogenesis is established at least as early as 8 weeks. Consequently, CAH girls have prolonged exposure to high fetal concentrations of androgens, particularly in association with severe CYP21A2.
b. Placental steroid sulfatase deficiency: X-linked ichthyosis (XLI) is a skin condition caused by the hereditary deficiency of the steroid sulfatase (STS) enzyme that affects 1 in 2000 to 1 in 6000 males. XLI manifests with dry, scaly skin and is due to deletions or mutations in the STS gene. XLI and can also occur in the context of larger deletions causing contiguous gene syndromes.Treatment is largely aimed at alleviating the skin symptoms. The major symptoms of XLI include scaling of the skin, particularly on the neck, trunk, and lower extremities. The extensor surfaces are typically the most severely affected areas.
c. A WNT4 mutation associated with Müllerian-duct regression and virilization in a 46, XX woman. WNT4 mutations in XX women lead to a syndrome characterized by absence of Müllerian duct derivatives and hyperandrogenism with or without renal anomalies, which is close to but is considered different from MRKH syndrome.
d. Aromatase Deficiency is a rare cause of fetal virilization. Aromatase deficiency is a condition resulting from insufficient production of the enzyme aromatase, which can lead to inappropriate virilization. One notable feature is that it can also affect the mother during gestation. Testosterone may be normal or elevated. The lack of estrogen results in the presentation of amenorrhea and tall stature; the latter occurs because estrogen normally causes fusion of the epiphyseal growth plates.
The following are examples of DSD classifications based on the new nomenclature:
1. Sex chromosome DSD
a. 45, X (Turner syndrome and variants)
b. 47, XXY (Klinefelter syndrome and variants)
c. 45, X/46, XY (mixed gonadal dysgenesis, ovotesticular DSD)
d. 46, XX/46, XY (chimeric, ovotesticular DSD)
2. 46,XY DSD
a. Disorders of testicular development (complete and partial gonadal dysgenesis)
b. Disorders of androgen synthesis (complete and partial androgen insensitivity, disorders of antimüllerian hormone [AMH]/receptor, androgen biosynthesis defect)
c. Other (severe hypospadias, cloacal exstrophy)
3. 46, XX DSD
a. Disorders of ovarian development (ovotesticular DSD, testicular DSD [e.g.SRY+], gonadal dysgenesis)
b. Androgen excess (fetal [eg, congenital adrenal hyperplasia (3beta-hydroxysteroid dehydrogenase/21-hydroxylase/11beta-hydroxylase deficiency), p450 oxidoreductase deficiency, glucocorticoid receptor mutation], fetoplacental [Aromatase deficiency, Oxidoreductase deficiency], maternal [virilizing tumors, androgenic drugs])
c. Other (vaginal atresia, cloacal anomalies, Labial adhesions, Uterine anomalies [MODY5], Mullerian agenesis/hypoplasia)